The overarching themes in the Cell Stress and Biophysical Therapies (CSBT) Program are to understand how stress response pathways influences malignant transformation of cells, and in turn, to understand the ability of malignant cells to subvert and overcome the stress they endure during growth and metastasis, processes that render them more resistant to cancer therapies. CSBT aims to reduce stress-induced malignant events and rationally modulate stress response pathways to better treat and prevent the development of aggressive cancers while protecting normal tissues and organs. Roswell Park is the only comprehensive cancer center in the nation with a CCSG Program devoted to the study of stress, and while the concept of stress covers many areas, a unifying strength of the CSBT Program is its efforts to understand diverse stresses in the framework of common and fundamental molecular mechanisms associated with cancer progression and therapeutic response and hence survivorship. CSBT Program research is organized in two Specific Aims, each of which is aligned with the strategic plans of Roswell Park: 1) to identify and target intrinsic stress response mechanisms in malignant cells and 2) to characterize the impact of physiological, environmental, and therapeutic stressors in the tumor bearing host, both systemically and within the tumor microenvironment. CSBT works very closely with other Programs, in particular DT, to translate these findings into the clinical arena. The program is co-led by Elizabeth Repasky, PhD, a laboratory scientist with wide expertise in translational research, and Anurag Singh, MD, a Radiation Oncologist, clinician- scientist who became a CSBT Program Co-Leader in February 2018. Drs. Singh and Repasky have complementary expertise that covers a broad swath of basic, translational and clinical applications of stress biology and oncology. The inherently collaborative structure of the CSBT Program is exemplified by a longstanding Program Project Grant led by Sandra Gollnick, PhD. The Program is comprised of 19 members (with 25 peer-reviewed projects) from 8 Roswell Park departments (Pharmacology & Therapeutics, Molecular & Cellular Biology, Cell Stress Biology, Surgical Oncology, Dermatology, Pathology, Immunology and Radiation Medicine) whose NCI funding is $2.4M, total peer-reviewed $2.7M, and total funding of $4.4M (project direct costs). The CSBT Program enjoys robust basic science research enhanced by inter-and intra-programmatic, national, and international research collaborations. Since the last review, NCI funding, peer-reviewed and total research support, has increased. Of the 282 publications generated over the last funding cycle, 10% were intra-programmatic, 36% were inter- programmatic collaborations and 81% inter-institutional, with 25 published in journals with an impact factor of 10 or greater. Training and mentoring opportunities for trainees and new investigators are provided within the CSBT Program. The CSBT Program has benefited from use of Shared Resources and support from the CCSG and Roswell Park. CSBT Program research is closely linked to cancers found in our catchment area.